Polymeric marker with high radiopacity for use in medical devices

ABSTRACT

High radiopacity is achieved in a polymeric marker by combining a polymeric resin, a powdered radiopaque agent having uniformly shaped particles of a specific particle size distribution and a wetting agent. The method to produce the marker calls for the blending and pelletization of these materials followed by extrusion onto support beading. The resulting supported tubing is subsequently cut to length with the beading still in place. After ejection of the beading remnant the marker is slipped into place on the device to be marked and attached by melt bonding. Marking of a guidewire allows lesions to be measured while the marking of balloon catheters allow the balloon to be properly positioned relative to a lesion.

CROSS-REFERENCES TO RELATED APPLICATION

This application is a division of currently pending U.S. patentapplication Ser. No. 10/945,637 filed Sep. 21, 2004, which is acontinuation-in-part of application Ser. No. 10/667,710, filed Sep. 22,2003, pending.

BACKGROUND OF THE INVENTION

The present invention is directed to elongated intracorporeal devices,and more particularly intraluminal devices for stent deployment,percutaneous transluminal coronary angioplasty (PTCA), and the similarprocedures. PTCA is a widely used procedure for the treatment ofcoronary heart disease. In this procedure, a balloon dilatation catheteris advanced into the patient's coronary artery and the balloon on thecatheter is inflated within the stenotic region of the patient's arteryto open up the arterial passageway and increase the blood flow throughthe artery. To facilitate the advancement of the dilatation catheterinto the patient's coronary artery, a guiding catheter having apreshaped distal tip is first percutaneously introduced into thecardiovascular system of a patient by the Seldinger technique throughthe brachial or femoral arteries. The catheter is advanced therein untilthe preshaped distal tip of the guiding catheter is disposed within theaorta adjacent the ostium of the desired coronary artery. A balloondilatation catheter may then be advanced through the guiding catheterinto the patient's coronary artery until the balloon on the catheter isdisposed within the stenotic region of the patient's artery.

Once properly positioned across the stenosis, the balloon is inflatedone or more times to a predetermined size with radiopaque liquid atrelatively high pressures (e.g., generally 4-12 atmospheres) to dilatethe stenosed region of a diseased artery. After the inflations, theballoon is finally deflated so that the dilatation catheter can beremoved from the dilatated stenosis to resume blood flow.

Similarly, balloon catheters may be used to deploy endoprostheticdevices such as stents. Stents are generally cylindrical shapedintravascular devices that are placed within a damaged artery to hold itopen. The device can be used to prevent restenosis and to maintain thepatency of blood vessel immediately after intravascular treatments.Typically, a compressed or otherwise reduced diameter stent is disposedabout an expandable member such as a balloon on the distal end of thecatheter, and the catheter and stent thereon are advanced through thepatient's vascular system. Inflation of the balloon expands the stentwithin the blood vessel. Subsequent deflation of the balloon allows thecatheter to be withdrawn, leaving the expanded stent within the bloodvessel.

Typically, the distal section of a balloon catheter or otherpercutaneous device will have one or more radiopaque markers in orderfor the operator of the device to ascertain its position and orientationunder X-ray or fluoroscopy imaging. Generally, a band or ring of solidradiopaque metal is secured about an inner or outer shaft of a ballooncatheter to serve as a radiopaque marker. Such configuration, however,locally stiffens the catheter shaft and thereby imparts an undesirablediscontinuity thereto as the solid metal bands are relatively inflexiblecompared to a polymer balloon catheter shaft. Additionally, the metallicmarkers are relatively expensive to manufacture and relatively difficultto positively affix to an underlying device.

As is described in U.S. Pat. No. 6,540,721, which is incorporated hereinby reference, many of the problems associated with the use ofconventional markers may be overcome by replacing the rigid preciousmetal tubing with a polymer that is filled or doped with a suitableradiopaque agent. Such marker may be formed by blending a polymer resinwith a powdered, radiographically dense material such as elementaltungsten and then extruding the composition to form a tubular structurewith an appropriate inner diameter and wall thickness. The extrusion maythen be cut to discrete lengths and installed onto the intendedcomponent via a melt bonding process.

A shortcoming of such an approach has been found to be the apparentlimit to which a suitable polymer can be filled with a radiographicallydense material to yield a composition that can be successfullycompounded, economically shaped into suitable dimensions for markers andeasily assembled onto a component without unduly compromising thedesirable properties of the polymer matrix. The fill ratio that isachievable will determine how thick a marker must be in order to achievea particular degree of radiopacity. In the case of tungsten in a polymersuch as Pebax (polyether block amide), the fill ratio limit hasheretofore been found to be about 80 weight percent. Such weightpercentage equates to about 18 volume percent which requires the markerto be excessively thick in order to achieve adequate radiopacity.

A polymeric marker is therefore needed having a substantially higherfill ratio than has heretofore been possible. Such marker would allowdevices to be rendered highly visible without an inordinate increase inoverall profile nor a compromise of the flexibility of the underlyingcomponent.

SUMMARY OF THE INVENTION

The invention is directed to a polymeric radiopaque marker for a medicaldevice.

The present invention overcomes the shortcomings of previously describedpolymeric radiopaque markers by enabling a polymer to be filled or dopedwith a considerably greater quantity of a radiopaque agent than hasheretofore been achievable. The increased fill ratio nonetheless allowsuniform pellets to be compounded and an extrusion with the appropriatewall thickness to be formed. The resulting marker provides anunprecedented combination of radiopacity and flexibility. Such markerwould allow any of various intraluminal devices to be radiopaquelymarked including, but not limited to, coronary and peripheral ballooncatheters, stent delivery catheters, and guiding catheters as well asguidewires.

The marker of the present invention relies on the use of radiopaquematerials with a preselected particle shape and a preselected particlesize distribution as well as the inclusion of one or more additives inthe polymer/radiopaque agent blend. A multifunctional polymeric additiveis added to the composition in order to enhance the wetting, adhesiveand flow properties of the individual radiopaque particles by thepolymer so as to cause each particle to be encapsulated by the polymerand thereby allow the polymer to form a continuous binder. Anantioxidant may optionally be added in order to preserve the highmolecular weight of the polymer matrix as it is exposed to the hightemperatures and shear stresses associated with the compounding andextrusion processes.

While previous attempts to increase fill ratios have involved tungstenpowder of relatively fine particle size, the present invention relies onthe use of particles of increased size in order to achieve such end. Anincrease in particle size has been found to allow the polymer to moreeffectively function as a continuous binder and thereby increaseductility at a given fill ratio or maintain ductility at increased fillratios. It has been found that in constraining the average particle sizeto at least 2 microns and limiting maximum particle size to about 20microns provides the desired results. In the case of tungsten in Pebax,a fill ratio of about 91.3 weight percent (equivalent to 36.4 volumepercent) or more is readily attainable for a polymeric marker formed inaccordance with the invention. In one embodiment, the fill ratio isabout 90.8 weight percent (34.9 volume percent) to about 93.2 weightpercent (42.7 volume percent). Additionally, it has been found that theprocess by which the tungsten powder is produced has a considerableeffect on both particle size distribution as well as the shape of theindividual particles. Tungsten powder produced by either a “pusher”process or “atomization” process, then milled and classified has beenfound to provide discrete particles having a more equiaxed shape andsize respectively and are therefore more ideally suited for the purposesof the present invention than powders produced employing a “rotary”process.

The marker of the present invention is manufactured by first tumblemixing the polymer resin with a pelletized wetting agent, such as maleicanhydride graft polyolefin resin (MA-g-PO), and an antioxidant and thenintroducing the mixture into the primary feeder of a twin screwextruder. The mixture is fed in at a controlled mass flow rate andconveyed down the barrel length as it is heated above its meltingtemperature and blended. At a point downstream, tungsten powder isintroduced into the mix at a controlled mass flow rate via a secondaryfeeder. The tungsten powder and the molten ingredients become intimatelyintermixed as they are conveyed downstream and discharged through a dieas molten strands which are cooled in water and subsequently pelletized.The markers are subsequently formed by extruding the tungsten filledpolymer onto a continuous beading of PTFE, and drawn down to yield thedesired wall thickness. The extrusion tolerances are such that the outerdiameter of the extrusion can vary by as much as 0.001 inch, which islarge enough to significantly affect the radiopacity and profile of thefinished marker. Consequently, in a presently preferred embodiment, theextrusion is hot die necked (i.e., the extruded tube on a supportmandrel, such as the PTFE beading, is pulled through a heated die totake on the die size), to resize the outer diameter and provide thedesired wall thickness. The extrusion is then cut to the desiredlengths, preferably with the beading still in place so as to providesupport. Removal of the beading remnant then allows the marker to beslipped onto the medical device or component thereof to be marked andmelt bonded in place. The polymeric marker is typically a closed,solid-walled band with a tubular or annular shape. However, thepolymeric marker can have a variety of suitable shapes. Reliance on meltbonding obviates the need for the marker to completely surround theunderlying device. Markers can for example be longitudinally split inhalf to form two markers of C-shaped cross-section. Or, solid strands ofextruded marker helical patterns.

During melt bonding, the polymeric marker is heated to an elevatedtemperature sufficient to melt the polymeric material to produce themelt bond. However, in one presently preferred embodiment, the elevatedtemperature is low enough to minimize or prevent flowing of thepolymeric material of the marker. Consequently, the double wallthickness (inner diameter minus outer diameter) of the polymeric markerafter melt bonding is equal to or not substantially less than (i.e., notmore than about 5 to about 25% less than) the double wall thicknessprior to melt bonding. Although some rounding of the edges of thepolymeric marker may occur during melt bonding, the maximum wallthickness of the polymeric marker is preferably not reduced during themelt bonding. The marker radiopacity is strongly affected by both thepercent loading of radiopaque material and the final wall thickness ofthe marker. Consequently, the percent loading of radiopaque material andthe wall thickness of the finished marker are carefully controlled toprovide the desired radiopacity. If the wall thickness of the polymericmarker is less than the required minimum wall thickness, the radiopacityof the marker will be too low. On the other hand, if the outerdiameter/wall thickness of the polymeric marker is greater than therequired maximum outer diameter/wall thickness, the large profile andadded stiffness of the marker will disadvantageously affect catheterperformance. Thus, the hot die necked extrusion has an outer diameterand wall thickness which is within the minimum and maximum desiredvalues, so that little or no thinning of the marker is required duringmelt bonding of the marker to provide the desired outer diameter. As aresult, a decrease in wall thickness which can reduce the radiopacity ofthe finished marker is prevented or minimized during bonding. In oneembodiment, the polymeric marker is adhesively bonded to the medicaldevice or component, and as a result, the wall thickness of the markeris not affected by the bonding process.

Due to its high radiopacity, flexibility and melt bondability, themarker of the present invention is readily attached to for example theinner member of a balloon catheter, a guidewire, and even a guidecatheter tip. The attachment of radiopaque markers of known dimensionsto a guidewire or the attachment to a guidewire of multiple radiopaquemarkers with known separation distances impart a measurement capabilityto the catheter that allows a physician to quickly and easily measurelesions and decide on appropriate stent lengths.

These and other features of the present invention will become apparentfrom the following detailed description of preferred embodiments which,taken in conjunction with the accompanying drawings, illustrate by wayof example the principles of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an enlarged side view of the radiopaque markers of the presentinvention attached to a balloon catheter;

FIG. 2 is an enlarged side view of radiopaque markers of the presentinvention attached to a guidewire in a preferred configuration; and

FIG. 3 is an enlarged side view of the radiopaque markers of the presentinvention attached to a guidewire in an alternatively preferredconfiguration.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention provides a radiopaque marker for use on a varietyof devices that is flexible, highly radiopaque and is easily attachableto such devices by melt bonding. These properties allow markers to be ofminimal thickness and thereby minimize the effect the marker has on theoverall profile and stiffness of the device to which it is to beattached.

In order to achieve the high fill ratios that are necessary to attainthe desired radiopacity and in order to do so without compromising thecompoundability and workability of the polymeric material nor itsultimate strength and flexibility, a number of different parameters havebeen found to be of importance. More specifically, both the particleshape and particle size of the radiopaque agent must be carefullycontrolled while the inclusion of a wetting agent such as MA-g-PO in thepolymer blend is critical. An antioxidant may additionally be includedin an effort to reduce the adverse effect the high processingtemperatures and shear stresses may have on polymer properties.

A number of polymeric materials are well suited for use in themanufacture of the markers of the present invention. The materialpreferably comprises a low durometer polymer in order to render themarker sufficiently flexible so as not to impair the flexibility of theunderlying medical device component to which the finished marker is tobe attached. Additionally, in one embodiment, the polymer is preferablycompatible with the polymeric material of which the component isconstructed so as to allow the marker to be melt bonded in place. Forexample, in one embodiment, the polymeric marker and at least an outerlayer of the catheter shaft are formed of the same class of the polymers(e.g., polyamides) so that they are melt bondable together. In anotherembodiment, the polymeric markers are installed on a dissimilar class ofpolymeric substrate, and are retained in position by adhesion ordimensional interference. The polymer must also impart sufficientstrength and ductility to the marker compound so as to facilitate itsextrusion and forming into a marker, its subsequent handling andattachment to a medical device and preservation of the marker'sintegrity as the medical device is flexed and manipulated during use.Examples of such polymers include but are not limited to polyamidecopolymers like polyether block amide (PEBAX), polyetherurethanes likePELLETHANE, polyester copolymers like HYTREL, olefin derived copolymers,natural and synthetic rubbers like silicone and SANTOPRENE,thermoplastic elastomers like KRATON and specialty polymers like EVA andabout 63D to about 25D is preferred. The preferred polymer for use inthe manufacture of a marker in accordance with the present invention ispolyether block polyamide copolymer (PEBAX), with a Shore durometer ofabout 40D. However, other classes of polymers allowing for lowerdurometers may be used in the radiopaque markers, such as polyurethanes,which may provide greater flexibility.

A number of different metals are well known to be radiographically denseand can be used in a pure or alloyed form to mark medical devices so asto render them visible under fluoroscopic inspection. Commonly usedmetals include but are not limited to platinum, gold, iridium,palladium, rhenium and rhodium. Less expensive radiopaque agents includetungsten, tantalum, silver and tin, of which tungsten is most preferredfor use in the markers of the present invention.

The control of particle size has been found to be of critical importancefor achieving the desired ultra high fill ratios. While efforts toincrease fill ratios have previously utilized small average particlesizes (1 micron or less) so as to minimize the ratio of particle size toas-extruded wall thickness, it has been found that higher fillpercentages can be realized with the use of somewhat larger averageparticles sizes. It is desirable in the formulation of high fill ratiocompounds to have the following attribute: 1) uniform distribution ofthe filler particles, and 2) continuity of the surrounding polymermatrix, and 3) sufficient spacing between filler particles so that thepolymer matrix provides ductility to the bulk mixture to impartprocessability in both the solid and molten state.

The use of larger average particle sizes results in greater spacingbetween filler particles at a given percentage, thus maintainingprocessability during compounding and especially subsequent extrusioncoating. The upper limit of average particle size is determined by thewall thickness of the coating and the degree of non-uniformity tolerable(i.e., surface defects). It has been found that a particle sizedistribution having an average particle size range of at least 2 micronsto 10 microns and a maximum particle size of about 20 microns yields thedesired fill ratio and provides for a smooth surface in the marker madetherefrom.

The control of particle shape has also been found to be of criticalimportance for achieving the desired ultra high fill ratios. Discreteparticles of equiaxed shape have been found to be especially effective,as individual particles of irregular shape, including agglomerations ofmultiple particles, have been found to adversely impact the surface, andthus, the maximum fill ratio that is attainable.

It has also been found that the process by which certain metal powdersare produced has a profound effect on the shape of the individualparticles. In the case of metallic tungsten, the powders may be formedby the reduction of powdered oxides through either “rotary,” “pusher” or“atomization” processing. Of these processes, “rotary” processing hasbeen found to yield the least desirable shape and size distribution aspartial sintering causes coarse agglomerates to be formed which do notbreak up during compounding or extrusion and thus adversely effect themarker manufactured therefrom. Atomized powders have been reprocessed bymelting and resolidifying “rotary” or “pusher” processed powders andresult in generally equiaxed, discrete particles which are suitable foruse in the present invention. “Pusher” processed powders are preferreddue to their low cost and discrete, uniformly shaped particles.

In order for the polymer to most effectively encapsulate individualradiopaque particles, it is necessary for a low-energy interface toexist between such particles and the polymer so as to enable the polymerto “wet” the surface of the particles. The materials should have similarsurface energies to be compatible. For materials which do not naturallyhave similar surface energies, compatibility can be promoted bygenerating a similar surface energy interface, i.e., a surface energyinterface which is intermediate between the natural surface energies ofthe materials. Certain additives such as surfactants and coupling agentsmay serve as wetting agents and adhesion promoters for polymer/metalcombinations that are not naturally compatible. It has been found thatadditives containing maleic anhydride grafted to a polyolefin backboneprovide a significant benefit in this regard wherein materialscommercially available as Lotader 8200 (having LLDPE Backbone) andLicomont AR504 (having PP backbone) were found to be particularlyeffective for use with tungsten/Pebax combinations. Emerging extrusionswere found to be less susceptible to breakage, and the melt viscosityduring compounding was lower as was manifested by a reduction in torqueexerted during the extrusion process. The use of such additives allowedcompounds with higher fill ratios to be successfully produced.

The inclusion of an antioxidant in the marker composition has also beenfound to be of benefit. Commercially available antioxidants such asIrganox B225 or Irganox 1010, have been found to minimize degradation(i.e., reduction in molecular weight) of the polymer matrix as it isexposed to the multiple heat and shear histories associated with thecompounding, extrusion, and bonding processes.

The compound used for the manufacture of the marker of the presentinvention is preferably made by first blending the polymer resin andwetting agent, and optionally, an antioxidant such as by tumble mixingafter which such blend is introduced into a twin-screw extruder via aprimary feeder. The feed rate is carefully controlled in terms of massflow rate to ensure that a precise fill ratio is achieved uponsubsequent combination with the radiopaque agent. The heat that thematerials are subjected as they are conveyed through the extruder causesthe polymer to melt to thereby facilitate thorough homogenization of allof the ingredients. The radiopaque agent powder, selected for itsuniform particle shape and controlled particle size distribution asdescribed above is subsequently introduced into the melt stream via asecondary feeder, again at a carefully controlled mass flow rate so asto achieve the target fill ratio. The solid powder, molten polymer andadditives are homogenized as they are conveyed downstream and dischargedthrough a die as molten strands which are cooled in water andsubsequently pelletized. The preferred extrusion equipment employs twoindependent feeders as introduction of all components through a singleprimary feeder would require significantly higher machine torques andresult in excessive screw and barrel wear. The powder feeder ispreferentially operated in tandem with a sidefeeder device, which inturn conveys the powder through a sealed main barrel port directly intothe melt stream. A preferred composition comprises a fill ratio of atleast 90.8 weight percent of tungsten (H. C. Starck's Kulite HC600s,HC180s and KMP-103JP) to Pebax 40D. A maleic anhydride source in theform of Licomont AR504 is initially added to the polymer resin at therate of approximately 3 pphr while an antioxidant in the form of CibaGeigy Irganox B225 at the rate of approximately 2 pphr (parts perhundred relative to the resin). The temperature to which materials aresubjected to in the extruder is about 221° C.

Once the marker material has been compounded, the marker can befabricated in suitable dimensions by an extrusion coating process. Whilefree extrusion is possible, this method is problematic due to the highfill ratios of the polymeric materials. Extrusion onto a continuouslength of beading has been found to lend the necessary support for themolten extrudate to prevent breakage. The support beading may take theform of a disposable, round mandrel made of PTFE (Teflon) coatedstainless steel wire or other heat resistant material that does notreadily bond to the extrudate. By additionally limiting the area drawdown ratio (ADDR) to below 10:1 the tungsten-laden melt can successfullybe drawn to size by an extrusion puller. The beading provides the addedbenefit of fixing the inner diameter and improving overall dimensionalstability of the final tungsten/polymer coating. Extrusions of a 91.3weight percent fill ratio tungsten/Pebax composition described aboveover 0.0215″ diameter PTFE beading were successfully drawn down to awall thickness of 0.0025″ to yield a marker properly sized forattachment to for example a 0.022″ diameter inner member of ballooncatheter. Also, extrusion coatings of 91% compound over 0.007″ tefloncoated stainless steel wire were successfully drawn down to single wallthicknesses of 0.002″ to make guidewire coatings.

In one embodiment, once the extrudate has cooled, the extrusion issimply cut to the desired lengths (e.g., 1 to 1.5 mm) of the individualmarkers, such as with the use of a razor blade and reticle, preferablywith the beading still in place to provide support during cutting. Thebeading remnant is subsequently ejected and the marker is slipped onto amedical device or a particular component thereof. In one embodiment, asegment of the extrudate is hot die necked with the beading inside toresize the outer diameter and wall thickness of the extrudate prior tocutting into individual markers. For example, an extrudate, having aninner diameter of about 0.0215±0.0005 inches and an outer diameter ofabout 0.0275±0.001 inches, is hot die necked to an outer diameter ofabout 0.0265 inches to produce a double wall thickness of about0.005±0.0005 inches. To minimize part to part variability in double wallthickness, the actual hot die size may be selected based upon the actualbeading diameter prior to hot die necking.

Finally, the marker is attached to the underlying substrate, preferablywith the use of heat shrink tubing and a heat source (hot air, laser,etc.) wherein the heat (˜171-210° C.) simultaneously causes the markerto melt and the heat shrink tubing to exert a compressive force on theunderlying molten material. To prevent extensive dimensional changes(e.g., thinning) of the polymeric marker, the temperatures used arebelow the melting temperature, thereby relying on heat and pressure tosoften the marker and generate an adhesive bond with the underlyingsubstrate. For markers formed of PEBAX 40D, the temperature used isabout 120-135° C. Heat bonding a marker onto an underlying componentprovides the added benefit of slightly tapering the edges of the markerto reduce the likelihood of catching an edge and either damaging themarker or the medical device during assembly or handling of the medicaldevice.

A marker formed as per the above described compounding, fabricating andassembling processes, having a fill ratio of 91.3 weight percent (36.4volume percent) with a wall thickness of 0.0025″ has been shown to havedramatically more radiopacity than commercially available 80 weightpercent compounds and comparable to the radiopacity of 0.00125″ thickconventional Platinum/10% Iridium markers. The radiopacity is a functionof the total volume of radiopaque material present in the marker (i.e.,the product of the volume % and the volume of the marker). In apresently preferred embodiment, the marker is about 1.5 mm long and hasa double wall thickness of about 0.0045 to about 0.0055 inches and afill ratio of about 90.8 to about 93.2 weight percent of tungsten, whichprovides a volume of radiopaque material substantially equal to thevolume of Platinum/10% Iridium in a 1.0 mm long, 0.0025 inches thick(double wall) conventional Platinum/Iridium marker band. Preferably, thevolume of radiopaque material is not less than about 30%, and the doublewall thickness of the marker is at least about 0.004 inches, to providesufficient radiopacity. However, as discussed above, the ability toincrease the volume of the marker by increasing the wall thickness ofthe marker is limited by the resulting increase in profile andstiffness. In a presently preferred embodiment, the double wallthickness of the marker is not greater than about 0.006 inches.

FIG. 1 illustrates two radiopaque markers 12 attached to the innermember 14 of a balloon catheter 16. During assembly of the catheter 16,the markers are attached to the inner member prior to the positioning ofthe inner member within the balloon 18 and attachment thereto at 20.Fluoroscopic illumination of the device allows the nonradiopaque balloonto be positioned relative to a lesion by virtue of the visibility of theradiopaque markers under fluoroscopy and their known positions relativeto the balloon. The balloon catheter 16 generally comprises an elongatedshaft having an inflation lumen and a guidewire lumen, and balloon 18with a proximal end and distal end sealingly secured to a distal sectionof the shaft and an interior in fluid communication with the inflationlumen. The shaft typically comprises an outer tubular member definingthe inflation lumen, and the inner tubular member 14 extending within atleast a portion of the inflation lumen and defining the guidewire lumen.

FIG. 2 illustrates a preferred embodiment of a guidewire with ameasurement feature 22 wherein a series of radiopaque markers 24 areattached to the core member of the guidewire 24 at preselectedseparation distances 26 to allow the device to be used as a type ofruler to measure the size of a lesion. The separation between adjacentmarkers may be controlled by the use of radiotransparent tubular spacers28 that are similarly adhered to the underlying guidewire. Upon assemblyof the radiopaque markers and the radiotransparent spacers onto at leasta distal section of the guidewire core member, heat shrink tubing ofsufficient length is slipped over the entire section of guidewire andheated to the appropriate temperature to cause both the markers as wellas the spacers to become adhered to the guidewire core member.

FIG. 3 illustrates an alternatively preferred embodiment of a guidewirewith a measurement feature 30 wherein an equally spaced series ofdifferently sized radiopaque markers 32 a-e are attached to the coremember of guidewire 34 to allow the device to be used to gauge the sizeof a lesion. The separation between adjacent markers may be controlledby the use of radiotransparent tubular spacers 36 that are similarlyadhered to the underlying guidewire. Upon assembly of the radiopaquemarkers and the radiotransparent spacers onto the guidewire core member,heat shrink tubing of sufficient length is slipped over the entiresection of guidewire and heated to the appropriate temperature to causeboth the markers as well as the spacers to become adhered to theguidewire core member.

While a particular form of the invention has been described, it will beapparent to those skilled in the art that various modifications can bemade without departing from the spirit and scope of the invention. Morespecifically, a variety of different polymers and radiopaque agents canbe compounded using the appropriate wetting agent, markers of differentshape and dimensions can be formed and the markers can be attached toany of a variety of medical devices that can benefit from beingradiopaquely marked. Accordingly, it is not intended that the inventionbe limited except by the appended claims.

1-11. (canceled)
 12. A method for manufacturing a radiopaque marker fora medical device, comprising: a) providing a polymer, and a wettingagent; b) causing said polymer to melt and to become intimatelyintermixed with said wetting agent; c) combining said molten polymer andwetting agent with radiopaque particles, wherein such particles compriseat least 30 volume percent of said combination and said particles havean average diameter of at least 2 microns and a maximum diameter ofabout 20 microns; d) extruding said combination onto support beading soas to form a coating thereon; and e) cutting said coating to preselectedlengths.
 13. The method of claim 12, wherein said polymer is caused tomelt and to become intimately combined with said wetting agent byconveyance through a compounding extruder.
 14. The method of claim 13,wherein said radiopaque particles are combined with said molten polymer,wetting agent, and an anti-oxident in said compounding extruder.
 15. Themethod of claim 12, wherein said combination is extruded such that it isdrawn while supported by said beading.
 16. The method of claim 12,wherein said combination is pelletized before being extruded onto saidsupport beading.
 17. The method of claim 12, wherein said polymercomprises polyether block amide, said radiopaque particles comprisetungsten, and said wetting agent comprises maleic anhydride graftpolyolefin. 18-47. (canceled)
 48. The method of claim 12 includingbefore (e) resizing the outer diameter of the extruded combination byhot die necking the extruded combination.
 49. The method of claim 18wherein the polymeric marker has a double wall thickness before meltbonding, and (c) comprises heating the polymeric marker to an elevatedtemperature which is sufficiently low so that the polymeric markerdouble wall thickness after melt bonding is equal to or notsubstantially less than the double wall thickness before melt bonding.50. The method of claim 49 wherein the elevated temperature is below themelting temperature of a polymeric material forming the polymericmarker. 51-55. (canceled)